Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study

This is a multicenter, prospective, observational trial. We will measure biomarkers and
determine thresholds that will predict increased risk for SOS in pediatric patients receiving
HCT or high intensity chemotherapy/irradiation with the future goal of a randomized,
interventional, open-label, multicenter trial that will test the preemptive use of
defibrotide for prevention of SOS in an enriched high-risk population.

Inclusion Criteria:

Age ≤ 18 years undergoing HCT for any reason who fulfill any ONE (1) of the following
criteria:

1. History of hepatic disease as defined by:

1. Viral hepatitis (i.e., hepatitis C virus [HCV])

2. Liver tumor before HCT

3. Hepatic fibrosis or cirrhosis before HCT as proven by liver biopsy

4. High aspartate aminotransferase (AST) (> 2x ULN) before HCT (pre-transplant
evaluation)

5. High alanine transaminase (ALT) (> 2x ULN) before HCT

6. High bilirubin (> 1.2x ULN) before HCT

2. HCT high-risk features including:

a. Conditioning with high-risk modalities including: i. Busulfan (BU)-containing
regimen particularly with oral BU + cyclophosphamide ii. TBI-containing regimen,
particularly cyclophosphamide + total-body irradiation (TBI) b. ≥ 2 HCT c. Allo-HCT
for leukemia > or = second relapse d. Unrelated donor (URD) HCT e. Human leukocyte
antigen (HLA) mismatch HCT (less than 10 of 10 for bone marrow/peripheral blood stem
cell [BM/PBSC] or anything less than 6 of 6 for UCB) f. Use of sirolimus + tacrolimus
prophylaxis for GVHD

3. High-risk disease states including:

1. Juvenile myelo-monocytic chronic leukemia (JMML)

2. Primary hemophagocytic lymphohistiocytosis (HLH)

3. Adrenoleukodystrophy

4. Osteopetrosis

4. Other high-risk features including:

1. Prior treatment with gemtuzumab ozogamicin

2. Use of hepatotoxic drugs 1 month before HCT and during HCT

3. Iron overload (i.e., thalassemia/sickle cell) with serum ferritin > 1000ng/ml

4. Deficit of ATIII, T-PA (i.e., < 30% normal values), and resistance to activated
protein C if clinical indication (these values do not have to be specifically
checked if no clinical history)

5. Young age < 2 years but more than 1 month

Exclusion Criteria:

Patients who are transplanted but do not fulfill any of the above mentioned criteria.